Abstract for: Modeling the hypothalamus-pituitary-adrenal axis: A review and extension
Multiple models of the hypothalamus-pituitary-adrenal (HPA) axis have been developed to endogenously capture the oscillations seen in the cortisol concentration and to examine HPA axis dysfunction. We reviewed the existing models, replicated, and compared them by finding their correspondence to a dataset consisting of ACTH and cortisol concentrations of 18 individuals. We found that existing models use different feedback mechanisms, vary in the level of details and complexities, and often offer contradictory conclusions, while none provides a great fit. We therefore re-calibrated the best performing model using partial calibration and individual fixed effects. Our estimated parameters reduced the mean absolute percent error by around 50% and offered the best fit among existing models of HPA axis dynamics. Our analysis also suggests that circadian and ultradian cycles are not created endogenously by the HPA axis feedbacks.